For Pesky Mosquitoes, the Latest Buzz Is Bad

Riverside, CA — For thousands of years, civilizations have dreaded
the high-pitched whine and irritating welts of mosquitoes — and
the deadly infections they carry.

Now UC Riverside researchers have made the reign of these supreme parasites
less secure. They’ve solved the nearly 70-year-old mystery of how
the repellent DEET deters mosquitoes and other bugs. Safer, cheaper and
more effective repellents are now feasible.

The research team identified the precise areas in the antennas of mosquitoes
that detect DEET, structures that have long eluded discovery. Using some
clever reverse-engineering, they then identified three chemicals that
also repel mosquitoes, but don’t dissolve plastics or pose toxicity
risks, like DEET can.

Moreover, the chemicals are already approved for other uses, and so can
be more quickly incorporated into repellents against mosquitoes and other
bugs. They’re also cheaper than DEET, said Anandasankar “Anand”
Ray, an associate professor of entomology, who led the research.

The all-UC Riverside study was published Wednesday in the scientific journal Nature.

There’s no way of knowing when the improved repellents will hit the
market, Ray said. But now that they’re known to exist, he said the
federal government, private industry and charitable organizations should
make them a priority.

The study builds on earlier research by Ray and colleagues about blocking
mosquitoes from sensing their prey. That study was published in 2011,
also in Nature.

There’s a growing need for improved repellents to fight mosquito-borne
diseases, said Emmanuel Theodorakis, a UC San Diego professor of chemistry
and biochemistry, who has studied chemicals that repel the bloodsuckers
and other pests. The research represents “a novel approach to the
rational design of insect repellents,” Theodorakis said, referring
to the reverse-engineering.

Malaria kills 1.2 million people worldwide each year, mostly in poor countries
with inadequate health care systems. Dengue, West Nile virus and yellow
fever are also major public health risks in many countries. West Nile
virus from mosquitoes is a concern in the United States.

“Insect repellents such as DEET, a compound developed by the U.S.
Army in 1946, are slowly becoming less effective as shields against these
insects and, given their inherent limitations, they are likely to become
obsolete in the near future,” Theodorakis said.

“The approach highlights the use of modern biological and computational
techniques that, in synergy with synthetic and medicinal chemistry, provide
the foundation for the identification of new and potent insect repellents.”

Ray and colleagues discovered the olfactory receptors that detect the presence
of DEET. Called Ir40a receptors, they line the inside of a part of the
antenna called the sacculus.

The team then screened 500,000 chemicals with a computer algorithm for
predicted activity against the receptors. They found nearly 200 potential
DEET substitutes, then tested 10 of the most promising for repellent activity.

Eight of these 10 strongly repelled flies, and four of those tested on
Aedes mosquitoes, carriers of yellow fever and dengue fever, also repelled
them, Ray said. Of the four, three are food additives already approved
by the U.S. Food and Drug Administration. But before these could be sold
as repellents, they must be certified by the U.S. Environmental Protection
Agency, Ray said. And for widespread use in poor countries, low cost is vital.

Many more chemicals remain to be tested, Ray said, and some of those could
repel mosquitoes far more strongly than DEET, he said.

Ray said the new research complements the 2011 Nature study on blocking
mosquitoes from detecting prey. That study described how mosquitoes can
be prevented from sensing carbon dioxide, which is a powerful lure. Every
exhaled breath emits carbon dioxide that mosquitoes can follow upwind
to the source.

While blocking that sensing doesn’t actually repel mosquitoes, Ray
said it stops them from congregating around people. This greatly reduces
the chances of being bitten. A company called Olfactor Laboratories in
San Bernardino has brought the technology to market in a wearable patch.

Combining the technologies could create an even stronger repellent, Ray said.

Meanwhile, Ray’s lab continues to study what chemicals draw mosquitoes
to their prey. Skin odors play a big role.

“While carbon dioxide is the primary cue that draws mosquitoes very
close, it’s well known that dirty socks, for example, or houses
where human beings are not present are attractive to mosquitoes,”
Ray said. “In the presence of carbon dioxide it becomes super-attractive.”

More effective mosquito lures can be made using these chemicals, he said.